Drug Safety

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Established and Emerging Immunological Complications of Biological Therapeutics in Multiple Sclerosis

  • Babak Soleimani
  • Katy Murray
  • David HuntEmail author
Review Article


Biologic immunotherapies have transformed the treatment landscape of multiple sclerosis. Such therapies include recombinant proteins (interferon beta), as well as monoclonal antibodies (natalizumab, alemtuzumab, daclizumab, rituximab and ocrelizumab). Monoclonal antibodies show particular efficacy in the treatment of the inflammatory phase of multiple sclerosis. However, the immunological perturbations caused by biologic therapies are associated with significant immunological adverse reactions. These include development of neutralising immunogenicity, secondary immunodeficiency and secondary autoimmunity. These complications can affect the balance of risks and benefits of biologic agents, and 2018 saw the withdrawal from the market of daclizumab, an anti-CD25 monoclonal antibody, due to concerns about the development of severe, unpredictable autoimmunity. Here we review established and emerging risks associated with multiple sclerosis biologic agents, with an emphasis on their immunological adverse effects. We also discuss the specific challenges that multiple sclerosis biologics pose to drug safety systems, and the potential for improvements in safety frameworks.


Compliance with Ethical Standards


No sources of funding were used to assist in the preparation of this review.

Conflicts of Interest

Katy Murray has received financial support from Merck Serono, Biogen, Genzyme Sanofi, Roche and Novartis pharmaceuticals for scientific meeting attendance and consultation fees. David Hunt and Babak Soleimani have no conflicts of interest relevant to this review.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Anne Rowling ClinicUniversity of EdinburghEdinburghUK
  2. 2.MRC Institute of Genetics and Molecular MedicineUniversity of EdinburghEdinburghUK

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